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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Susceptibility to apoptosis is an essential prerequisite for successful eradication of tumor cells by chemotherapy. Consequently, resistance to apoptosis has been established as one of the mechanisms responsible for the failure of therapeutic approaches in many types of cancers. In the present study, we investigated the susceptibility of human lung cancer H460 cells to apoptotic cell death induced by cisplatin and determined its regulatory mechanisms. Treatment of the cells with cisplatin induced rapid generation of multiple oxidative species and a concomitant increase in apoptotic cell death. Apoptosis induced by cisplatin was mediated through the mitochondrial death pathway, which requires caspase-9 activation and is regulated by Bcl-2. Cisplatin induced down-regulation of Bcl-2 through a process that involves dephosphorylation and ubiquitination of the protein, which facilitates its degradation by proteasome. This down-regulation was inhibited by antioxidant enzymes catalase and glutathione peroxidase (H(2)O(2) scavenger), but not by superoxide dismutase (O(2)(.) scavenger) or deferoxamine (OH. inhibitor). Electron spin resonance and flow cytometric analyses showed the formation of H(2)O(2) along with O(2)(.) and OH. radicals after cisplatin treatment. H(2)O(2) was generated in part by dismutation of O(2)(.) and served as a precursor for OH.. Together, our results indicate an essential role of H(2)O(2) in the regulation of Bcl-2 and apoptotic cell death induced by cisplatin. Because aberrant expression of Bcl-2 has been associated with death resistance of cancer cells to chemotherapy, the results of this study could be used to aid the design of more effective strategies for cancer treatment.
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PMID:Peroxide is a key mediator of Bcl-2 down-regulation and apoptosis induction by cisplatin in human lung cancer cells. 1791 32

We investigated the involvement of glutathione (GSH) and reactive oxygen species (ROS) such as H2O2 and O2-* in the deaths of pyrogallol-treated Calu-6 cells. Pyrogallol inhibited the growth of Calu-6 cells with an IC50 of approximately 50 microM. Levels of intracellular H2O2 were not altered or were decreased in pyrogallol-treated Calu-6 cells at 72 h. However, levels of O2*- were increased. Treatment with pyrogallol also reduced the intracellular GSH content. The activity of SOD was down-regulated, but the activity of catalase was up-regulated by pyrogallol at 72 h. ROS scavengers, including Tempol, Tiron, Trimetazidine, and N-acetylcysteine (NAC), did not reduce the levels of the intracellular O2*-. Tempol showing the recovery of GSH depletion in pyrogallol-treated cells significantly prevented apoptosis, while Tiron prevented the loss of mitochondrial transmembrane potential (DeltaPsi(m)). In contrast, treatment with NAC showing an increased effect on O2*- levels and depletion of GSH intensified pyrogallol-induced apoptosis. In addition, treatment with SOD and catalase significantly prevented the loss of mitochondrial transmembrane potential (DeltaPsi(m)) in pyrogallol-treated Calu-6 cells. However, only catalase showing a decreased effect on O2*- levels and depletion of GSH prevented pyrogallol-induced apoptosis. Taken together, apoptosis in pyrogallol-treated Calu-6 cells is correlated with the changes of intracellular GSH levels rather than ROS levels.
Lung Cancer 2008 Mar
PMID:Apoptosis in pyrogallol-treated Calu-6 cells is correlated with the changes of intracellular GSH levels rather than ROS levels. 1792 Jul 21

The modulatory efficacy of capsaicin on lung mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, key citric acid cycle enzymes and respiratory chain enzymes during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice was studied. Elevations in mitochondrial LPO along with decrements in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, vitamin E and vitamin A), citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha-ketoglutarate dehydrogenase (alpha-KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and respiratory chain enzymes (NADH dehydrogenase and Cytochrome c oxidase) were observed in B(a)P (50mg/kg body weight) administered animals. CAP (10mg/kg body weight) pretreatment decreased lung mitochondrial LPO and augmented the activities of enzymic, non-enzymic antioxidants, citric acid cycle enzymes and respiratory chain enzymes to near normalcy revealing its chemoprotective function during B(a)P induced lung cancer.
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PMID:Stabilization of pulmonary mitochondrial enzyme system by capsaicin during benzo(a)pyrene induced experimental lung cancer. 1802 35

Chemoprevention has emerged as a very effective preventive measure against carcinogenesis. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on benzo(a)pyrene (B(a)P) induced carcinogenesis. In the present study, the efficacy of quercetin on the level of lipid peroxides, activities of antioxidant enzymes and tumor marker enzymes in B(a)P induced experimental lung carcinogenesis in Swiss albino mice was assessed. In lung cancer bearing animals there was an increase in lung weight, lipid peroxidation and marker enzymes such as aryl hydrocarbon hydroxylase, gamma glutamyl transpeptidase, 5'-nucleotidase, lactate dehydrogenase and adenosine deaminase with subsequent decrease in body weight and antioxidant enzymes-superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, reduced glutathione, vitamin E and vitamin C. Quercetin supplementation (25 mg/kg body weight) attenuated all these alterations, which indicates the anticancer effect that was further confirmed by histopathological analysis. Overall, the above data shows that the anticancer effect of quercetin is more pronounced when used as an chemopreventive agent rather than as a chemotherapeutic agent against B(a)P induced lung carcinogenesis.
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PMID:The effects of quercetin on antioxidant status and tumor markers in the lung and serum of mice treated with benzo(a)pyrene. 1805 10

The effect of a pungent ingredient of red pepper, capsaicin, on oxidative stress induced changes in the antioxidant defense system by benzo(a)pyrene in the lungs of mice was studied. Oral gavage administration of benzo(a)pyrene (50 mg/kg body weight) to mice led to a marked increase in oxidative stress indicated by alterations in pulmonary lipid peroxidation, enzymic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (reduced glutathione, vitamin C, vitamin E and vitamin A). Pre-co-treatment with capsaicin (10 mg/kg body weight i.p.) restored cellular normalcy, highlighting the antioxidant potential of capsaicin in mitigating the oxidative stress mediated damage produced during benzo(a)pyrene-induced lung cancer.
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PMID:Capsaicin modulates pulmonary antioxidant defense system during benzo(a)pyrene-induced lung cancer in Swiss albino mice. 1833 64

Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of cancer. Several bioactive compounds present in fruits and vegetables have revealed their cancer curative potential on lung cancer. Hesperidin is one such naturally occurring flavonoid widely found in citrus fruits. The aim of the present study is to divulge the chemopreventive nature of hesperidin during benzo(a)pyrene (B(a)P) induced lung cancer in Swiss albino mice. Administration of B(a)P (50 mg/kg body weight) to mice resulted in increased lipid peroxides (LPO), lung specific tumor marker carcinoembryonic antigen (CEA) and serum marker enzymes aryl hydrocarbon hydroxylase (AHH), gamma glutamyl transpeptidase (GGT), 5'nucleotidase (5'ND) and lactate dehydrogenase (LDH) with concomitant decrease in the levels of tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin E and vitamin C. Hesperidin supplementation (25 mg/kg body weight) significantly attenuated these alterations thereby showing potent anticancer effect in lung cancer. Further the antiproliferative effect of hesperidin was confirmed by histopathological analysis and proliferating cell nuclear antigen (PCNA) immunostaining. Overall, these findings substantiate the chemopreventive potential of hesperidin against chemically induced lung cancer in mice.
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PMID:Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice. 1870 64

Epidemiological evidence indicated that there was a synergistic interaction between arsenic and cigarette smoke on enhancement of lung cancer risk. Benzo[a]pyrene (B[a]P), a component in cigarette smoke, is one of the most carcinogenic compounds known. Animal studies have demonstrated that there were increased benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) adduct formation and lung tumorigenesis in animals when they were coexposed to B[a]P and arsenic. Since BPDE adduct is a by-product of B[a]P metabolism, elevation of B[a]P metabolism by arsenic is suspected. However, the effects of arsenic on cytochrome P450 1A1 (CYP1A1) status (expression and activity), which is essential for B[a]P metabolism, either in lung cells or in lung tissues, are never demonstrated. We hypothesized that arsenic would enhance aryl hydrocarbon receptor (AhR) activation leading to CYP1A1 expression and activity in lung cells. Indeed, our present study successfully demonstrated the elevation of CYP1A1 messenger RNA expression in H1355 cells, a human lung adenocarcinoma cell line, as well as CYP1A1 expression and activity in lung tissues of arsenic-exposed mice. We further demonstrated that this elevation of CYP1A1 expression could be effectively blocked with AhR antagonist, 3',4'-dimethoxyflavone, indicating that the arsenic-induced CYP1A1 expression and activity were via AhR activation. Furthermore, we found that arsenic-induced AhR activation and -enhanced CYP1A1 expression can be further increased by a prooxidant, buthionine-(S,R)-sulfoximine, and suppressed by antioxidants, such as N-acetylcysteine and catalase. Our findings provided clear evidence that arsenic can enhance CYP1A1 expression and activity via AhR activation, and the arsenic-induced AhR activation is probably triggered by oxidative stress.
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PMID:Involvement of oxidative stress and activation of aryl hydrocarbon receptor in elevation of CYP1A1 expression and activity in lung cells and tissues by arsenic: an in vitro and in vivo study. 1903 95

Antimycin A (AMA) inhibits the mitochondrial electron transport between cytochromes b and c. However, the relationship between AMA and lung cancer cells is poorly understood. In this study, we investigated the involvement of reactive oxygen species (ROS) and glutathione (GSH) in AMA-treated lung cancer Calu-6 cell death. Treatment with AMA reduced cell viability in a dose-dependent manner for 72 h. The intracellular ROS levels were decreased in Calu-6 cells treated with low doses of AMA (10, 25 or 50 microM) at 72 h. However, the levels increased in cells treated with a high dose of 100 microM AMA. Levels of O2.- were significantly increased in AMA-treated cells at 72 h. The increases in ROS levels including O2.- in AMA-treated cells were observed within 10 min. Treatment with AMA reduced the intracellular GSH content. SOD activity was up-regulated in AMA-treated Calu-6 cells at 72 h. However, catalase activity was down-regulated by AMA. Treatment with tiron, a ROS scavenger, reduced the intracellular ROS levels, which were associated with a partial reduction of apoptosis. Treatment with exogenous SOD and catalase significantly inhibited loss of the mitochondrial transmembrane potential (DeltaPsim) in AMA-treated Calu-6 cells. In conclusion, our results suggest that the changes of intracellular ROS and GSH affect apoptosis in AMA-treated Calu-6 cells.
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PMID:Tiron, a ROS scavenger, protects human lung cancer Calu-6 cells against antimycin A-induced cell death. 1908 70

Antimycin A (AMA) inhibits mitochondrial electron transport between cytochrome b and c. We recently demonstrated that AMA inhibits the growth of lung cancer Calu-6 cells and the changes of reactive oxygen species (ROS) and glutathione (GSH) levels affect apoptosis in Calu-6 cells. Here, we examined the effects of N-acetyl-cysteine (NAC, a well known antioxidant), L-buthionine sulfoximine (BSO, an inhibitor of GSH synthesis), diethyl-dithiocarbamate (DDC, an inhibitor of Cu, Zn-SOD) or 3-amino-1,2,4-triazole (AT, an inhibitor of catalase) on AMA-treated Calu-6 cells in relation to cell death, ROS and GSH levels. Treatment with AMA induced cell growth inhibition, apoptosis and the loss of mitochondrial membrane potential (MMP) (DeltaPsim) in Calu-6 cells. While the intracellular ROS level was decreased in 50 microM AMA-treated Calu-6 cells, O2.- levels among ROS were significantly increased. AMA also induced GSH depletion in Calu-6 cells. Treatment with NAC showed decreasing effect on O2.- levels in AMA-treated cells preventing apoptosis, MMP (DeltaPsim) loss and GSH depletion in these cells. BSO significantly increased GSH depletion and apoptosis in AMA-treated cells. While both DDC and AT increased ROS levels in AMA-treated Calu-6 cells, only DDC intensified GSH depletion and apoptosis. BSO and AT increased the ROS level in Calu-6 control cells, but these agents did not induce apoptosis and GSH depletion. In conclusion, our results suggest that GSH depletion rather than ROS level in AMA-treated Calu-6 cells is more tightly related to apoptosis.
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PMID:The effects of N-acetyl cysteine, buthionine sulfoximine, diethyldithiocarbamate or 3-amino-1,2,4-triazole on antimycin A-treated Calu-6 lung cells in relation to cell growth, reactive oxygen species and glutathione. 1957 81

Despite advances in anticancer treatment, lung cancer still has poor prognosis. Recently, a cancer stem cell (CSC) hypothesis has emerged describing a small subset of tumor cells with stem cell properties. CSCs found in many solid tumors express CD133 antigen on the cell surface. The presence of CSC is correlated with poor survival of patients with glioblastomas, colon or prostate cancers. In this study, we evaluated whether CD133 expression in non-small cell lung cancer (NSCLC) has a prognostic value in patients' survival. We also analyzed whether CD133 positivity of NSCLC correlates with the expression of resistance-related proteins, angiogenic factors, oncogenes, proliferative activity or apoptosis. CD133 expression was retrospectively examined in a total of 88 cases of previously untreated NSCLC by immunohistochemistry. We found no correlation between CD133 positivity or the amount of CD133(+) cells with NSCLC patients' survival, expression of oncogenes c-myc, c-N-ras, c-jun, c-fos, c-erbB1, c-erbB2 or p53, angiogenic factors VEGF, VEGFR-1, FGF, FGFR-1, tissue factor and with proliferative activity or apoptosis in NSCLC tissues. However, there was a significant association between the expression of resistance-related proteins glutathione S-transferase, thymidylate synthase, catalase, O(6)-methylguanine-DNA methyltransferase and p170 and CD133. Because CD133 expression is linked to a resistant phenotype, detection of CD133(+) cells may be useful to predict efficacy of cytotoxic therapy but CD133 is not a strong prognostic parameter for survival of patients with NSCLC.
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PMID:CD133 is indicative for a resistance phenotype but does not represent a prognostic marker for survival of non-small cell lung cancer patients. 1967 44


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